ESPE Abstracts

Introduction: Wolf-Hirschhorn syndrome (WHS) is a rare congenital disorder characterised by a "Greek-warrior-helmet" nasal appearance, growth delay, intellectual disability, and seizures. Limited studies exist on the growth evolution of WHS children, particularly regarding growth hormone (GH) therapy. We report a case of a 3-year-old boy with WHS and severe short stature.

Case Report: A 3-year-old male child, second born from non-consanguineous parents (mid-parental height 56.36 percentile, Z-score=0.16 SDS), presented to our clinic for short stature. Medical history revealed WHS and 15q13.2-13.3duplication. He was under Topiramate and Nitrazepam treatment for seizures. Physical examination revealed a short stature of 79 cm (-3,7 SDS) and 7,9 kg (-5.67 SDS) on the CDC 2- to 20-year growth charts and 0 SDS on WHS charts. Hormonal investigations revealed the following: GH 2.57 ng/ml (RR 0-6.3 ng/ml), IGF‐1 175 ng/ml (RR 13.9-104), IGF-BP3=4.91 (0.8-3.9). Other hormone profiles (TSH, FT4, and basal cortisol) were within normal ranges. Regarding the GH/IGF-1 axis results, IGF-1 insensitivity syndrome was suspected. He would be eligible for GH treatment as he was born small for gestational age. However, he does not meet all our national therapy protocol criteria because of the increased IGF-1 values association. At the most recent follow-up visit conducted after a five-month interval from the initial evaluation, he was stable on CDC and WHS growth charts (-3.67 SDS vs 0 SDS). Hormonal labs were consistent with the suspected diagnosis: IGF-1 levels at 168.8 ng/mL (RR 18.9-116 ng/ml), IGF-BP3 levels at 4.03 mcg/ml (RR 0.8-3.9) and basal GH levels at 0.237 ng/mL (RR 0.094-6.29). Furthermore, an X-ray of the hand indicated a delayed bone age of approximately 2-2.3 years.

Conclusion: GH therapy in patients with WHS leads to significant height increases during the prepubertal period but shows limited improvement in final height. Considering the limited success of GH treatment in improving the final height, treatment decision in WHS patients is challenging. In this patient, the challenge is further complicated because of the IGF-1 insensitivity association. Future research should explore the risk-benefit ratio of GH treatment in WHS patients, especially those with IGF-1 insensitivity, aiming to optimise treatment outcomes and reassess eligibility criteria. Additionally, investigating the association between WHS, 15q13.2-13.3 duplication, and IGF-1 insensitivity syndrome is essential for improving management strategies.